The heat from summertime weather will soon be here and so will the heat generated from grilling/barbequing, a favorite form of cooking during the summer. During the summer months tens of millions of Americans fire-up outdoor grills/barbeques, especially during favorite grilling holidays such as Fourth of July, Memorial Day and Labor Day. According to the Hearth, Patio & Barbeque Association (2007), “a majority of grill owners use their grills year-round and 44 percent use their grill 1-2 times per week during the peak grilling season (May-August)” (p. 1).

What, you may ask, could possibly be the health concerns associated with summertime barbeques or grilling at any time of the year for that matter? Well, according to some health and medical researchers, grilling (including broiling and pan frying) muscle meats (i.e., beef, pork, chicken and fish) at high temperatures produce worrisome chemicals called heterocyclic amines (HCAs), which some research suggests are mutagenic (i.e., capable of causing a mutation or structural damage to DNA) or otherwise associated with the formation of cancer cells in various organ tissues of the human body.

The April, 2016, issue of Health and Wellness Monthly is intended to help health consumers understand the nature of and potential health risks associated with diet-derived HCAs, four important factors responsible for the forming of HCAs and ways to protect against health-raising risks of HCAs.[1]

What Are Heterocyclic Amines?

HCAs are potent, mutagenic compounds created by using the high-temperature cooking methods of grilling/barbecuing, broiling or pan frying such foods as meats, poultry and fish, whole foods containing relatively high amounts of protein and creatine. Because of their protein content, cooking eggs at high temperatures can also result in the formation of HCAs. Investigators have isolated 17 different HCAs resulting from the grilling, broiling and pan frying of meats, poultry and fish (see National Cancer Institute – U.S. Institutes of Health, 2008). Four HCAs gaining the attention of researchers, while making the U.S. Department of Health and Human Services’ 11th Report on Carcinogens (RoC) are[2]:

2-Amino-3-Methylimidazo [4,5-f] quinoline (IQ)

2-Amino-3,4-dimethylimidazo [4,5-f] quinoline (MeIQ)

2-Amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx)

2-Amino-1-methyl-6- phenylimidazo [4,5-b]pyridine (PhIP)

Exposure to HCAs

It is important for health consumers to learn about how they can become exposed to HCAs and the estimated exposure levels. Exposure to HCAs, generally, and MelQ, MelQx, IQ and PhlP, specifically, is achieved primarily through the consumption of meats, poultry and fish cooked at high temperatures. However, scientists have detected HCAs in processed food-flavorings, beer, wine and cigarette smoke. Occupationally speaking, cooks can become exposed to HCAs through the inhalation of aerosolized particles created during the process of cooking foods high in protein (U.S. Department of Health and Human Services, 2005).

It is reported in the 11th RoC that the estimated dietary exposure to total HCAs ranges from less than one to 17 ng/kg (i.e., nano grams per kilogram) of body weight per day. In terms of the total HCA concentrations in cooked meat, the range is from less than one to approximately 500 ng/g (0.001 to 0.5 parts per million) but the concentrations are typically less than 100 ng/g.

Furthermore, pan residues usually have higher HCA concentrations than the cooked meat. Thus, when making gravy from meat drippings and grease, it is important to know that the gravy will contain relatively high concentrations of HCAs. Occupationally speaking, cooks can become exposed to HCAs through the inhalation of aerosolized particles created during the process of cooking foods high in protein (See U.S. Department of Health and Human Services, 2005).

Generally speaking, HCAs are considered potent, mutagenic compounds when it comes to non-humans. Numerous experimental studies with lab animals (e.g., mice & rats) show that HCAs are cancer-causing chemicals. For example, in mice and rats, the oral administration of MelQ caused tumors to develop in the forestomach of males and in the cecum, colon and liver of females. In male and female rats, the oral administration of MelQ caused cancerous tumors to develop in the colon, oral cavity and Zymbal gland.

The carcinogenicity of MelQx was demonstrated with its oral administration and the development of cancerous tumors in multiple tissue sites (e.g., liver tumors in males and females, lung tumors in females & lymphoma and leukemia in males) of mice and in rats with the formation of liver and Zymbal-gland tumors in males and females, skin tumors in males, and clitoral-gland tumors in females.

With respect to the two other HCAs in the RoC, IQ and PHlP caused tumors in multiple tissue sites in experimental mice, rats and monkeys for the former and mice and rats for the latter.

In addition to experimental animal models, HCAs have been shown to be mutagenic agents using what is called the Ames test. As it turns out, approximately 80%-85% of compounds identified as mutagenic with the Ames test are carcinogenic in experimental animals. Moreover, the potency of Ames tested agents determined to be mutagenic correlate with the carcinogenic potency of those agents (see Cattlemen’s Beef Board and National Cattlemen’s Beef Association, 2003).

Whether the findings from experimental studies using animal models and the Ames test can be extrapolated to humans is, according to many researchers, an open empirical question. Furthermore, although a body of evidence from epidemiological studies suggests that HCAs are mutagenic and carcinogenic in humans, researchers are not inclined to assert definitively that HCAs cause cancer in humans.

The reluctance to characterize HCAs as known cancer-causing agents in humans is due primarily to methodological reasons pertaining to experimental animal studies (e.g., lab animals are fed far greater amounts of HCAs per pound of body weight compared to humans eating meats, poultry and fish cooked at high-temperatures) and methodological issues associated with epidemiological studies (e.g., inability to control for confounding lifestyle variables capable of causing cancer in humans).

The more conservative approach in identifying HCAs as causing cancer in humans is reflected in the way the U.S. Department of Health and Human Services (2005), describes the four HCAs listed in its RoC. All four HCAs are described in the report as “reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity in experimental animals and supporting genotoxicity data” (U.S. Department of Health & Human Services, 2005, p. 1).

Nevertheless, although the carcinogenic effect in humans remains to be established and elucidated definitively, published epidemiological studies, according to the U.S. Department of Health and Human Services (2005), indicate that there is a human cancer risk related to the consumption of meats, poultry and fish prepared with high-temperature cooking methods such as grilling, pan-frying or broiling. Moreover, even though HCAs are present in foods (especially cooked meats) in micrograms per gram (a seemingly small amount) human exposure to HCAs is chronic because they are consumed (sometimes daily) over a lifetime. HCAs are readily absorbable and bioavailable compounds in humans and are metabolized relatively easily into derivatives that are potentially mutagenic and carcinogenic. Still further, some people are more genetically predisposed to transform or metabolically activate HCAs into genotoxic (DNA damaging) and cancer-causing agents (e.g., see Gooderham et al., 2001).

Thus, it would be prudent for those consuming meats, poultry and fish cooked at intense temperatures to be mindful of the potential cancer-causing risks in eating such foods and to take the necessary measures to modulate the formation of HCAs, lower their exposure and to protect themselves against them once entering their bodies.

Four Factors Affecting the Formation of HCAs

Type of food, cooking method/contact with heat source, temperature and amount of cooking time are four factors affecting the formation of HCAs. Foods high in protein and creatine are especially susceptible to the creation of HCAs (e.g., meats, poultry and fish).

Foods cooked by grilling, broiling and pan frying put the food in close contact with the heat source. These cooking methods tend to produce higher concentrations of HCAs than other cooking methods such as stewing, braising, roasting or microwaving.

Most experts consider temperature to be the most important factor in the formation of HCAs. High protein foods cooked at temperatures below 325 degrees produce low and even undetectable levels of HCAs. As the temperature rises, the potential for the formation of HCAs increases such that pan-fried ground beef cooked at a temperature of 425 degrees has six to seven more times mutagenic activity than pan-fried at 390 degrees (see Cattlemen’s Beef Board and National Cattlemen’s Beef Association, 2003).

Lastly, the more time foods are cooked at high temperatures the more HCAs which are formed. Ironically, hamburgers cooked in fast food restaurants tend to have low levels of HCAs because they are cooked for relatively quick using moderate temperatures (see Cattlemen’s Beef Board and National Cattlemen’s Beef Association, 2003).

Cooking Strategies Reducing the Formation of HCAs

Effective methods for minimizing the formation of HCAs have been mentioned in several studies (see U.S. Department of Health & Human Services, 2005). The following eight strategies from the Cattlemen’s Beef Board and National Cattlemen’s Beef Association (2003) are useful tips to minimize the formation of HCAs and tend to summarize the more important recommendations found in the literature:

Use moderate to low heat settings (e.g., 300-325 degrees Fahrenheit); cook as far away as possible from the heating element (e.g., a flame), and do not overcook or char MPF (meats, poultry & fish). This will be best for flavor, too!

When possible, choose cooking methods such as stewing, simmering, braising, microwaving, or deep-frying which do not induce formation of HAs. Only low levels of HAs form during baking/roasting. grilling/barbecuing, broiling, and pan-frying are the main cooking methods that can lead to formation of HAs.

When roasting, do not make gravy from the meat drippings.

When grilling, use medium to low temperature coals. (Cautiously hold the palm of your hand above the coals at cooking height. You will be able to hold your hand there for 4-5 seconds before the heat forces you to pull away if the goals are medium to low temperature).

Consider using grilling as a method of finish cooking. Microwave meats and poultry first for a few minutes and discard the “juices” before immediately placing the food on the barbecue for a short time. Microwave hamburger patties for 1 or 2 minutes, pour off the juice, and then grill, broil, or fry.

When grilling, use small pieces of MPF (e.g., skewered portions) to shorten cooking time.

Marinate meat or coat meat with breadcrumbs before grilling or frying.

Frequently turn ground beef patties when cooking (p. 8).

Conclusion

Although findings from experimental animal studies and Ames tests designed to determine the mutagenic and carcinogenic potential of HCAs cannot be applied directly to humans, the body of evidence generated from human and non-human research on HCAs, along with the consumption of HCAs over a lifetime and genetic factors predisposing people to convert HCAs into mutagenic (DNA damaging) and cancer-causing agents suggests that people lower their exposure and potential cancer risk due to HCAs.

One way to accomplish this goal this summer and throughout the year is to put into practice the offered recommended cooking strategies to minimize the creation of HCAs when cooking foods high in protein and creatine at high temperatures using the methods of grilling, broiling and pan frying.

Epidemiological studies reveal the incidence of cancer in humans is correlated with different factors (e.g., lifestyle, occupation, iatrogenic factors – exposure to drugs & radiation & cryptogenic factors – exposure to viruses). The lifestyle factors of diet and tobacco-use together account for approximately 70% of all human cancer, with diet by itself accounting for 35%-45% of human cancer (see Goodherham et al., 1996). With respect to dietary factors, daily diets high in saturated fat, low fiber and high in well-done meats tend to predispose individuals to cancer of the colon, breast, pancreas, prostate and endometrium (Goodherham et al., 1996).

Until scientists can determine with more empirical precision and biological certainty, the cancer-causing risk of HCAs for humans, it would be prudent to minimize one’s exposure to HCAs. In the world of science, what is ambiguous at one point becomes more apparent at another. Better to be safe than sick. Limit your intake of HCAs.

U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program (2005). Report on Carcinogens, Eleventh Edition. Washington, DC: U.S. Department of Health and Human Services.

[1] The article is being reissued so as to coincide with recent and upcoming broadcasts on Let’s Talk Nutrition focusing on summer health.

[2] HCAs are treated in this article as a general category of carcinogens. Readers can find an in-depth discussion of these four HCAs in the 11th Report on Carcinogens (U.S. Department of Health & Human Services, 2005) in terms of their carcinogenicity, properties, use, production and exposure.

[3] A carcinogen is any cancer-causing substance or agent. Carcinogenicity is the ability of a carcinogenic substance or agent to create cancer cells from normal cells.